A number of new protocols were introduced to examine brain aging and cerebral metabolism. In using the isotope fluoro-18-deoxyglucose with positron emission tomography, we found that cerebral glucose utilization does not change with advancing age in healthy males, but changes are found in patients with Alzheimer's disease and Down syndrome. Four new protocols allow us to evaluate these findings and determine their specificity. Studies are underway in multi-infarct dementia, the second leading cause of dementia; a major depressive disorder both with and without cognitive impairment; and fragile-X syndrome to evaluate PET alterations uncovered in our laboratory in subjects with Down syndrome. We also are studying healthy adult subjects with hypertension who have no symptomatic cognitive impairment. Blood has been collected from healthy controls, patients with Alzheimer's disease, and unaffected first degree relatives of patients with Alzheimer's disease. The buffy coat of this blood will be intracerebrally inoculated into hamsters to determine if Alzheimer's disease is transmissible. The role of the dopaminergic system in normal aging, Alzheimer's disease with and without extrapyramidal signs, and familial inverted chorea will be explored with 6-[18-F]-fluoro-L-Dopa (6-FD) and positron emission tomograph) (PET).